Although there has been sustained interest in the field of C-H bond oxidation, there is still a need for new methods and strategies for the functionalization of Csp3-H bonds in complex hydrocarbon systems. Within the context of a two-phase approach to terpene synthesis (a logic derived from the biosynthetic pathway of complex terpenoids), the carbogenic framework generated in the synthetic cyclase phase would be subjected to a series of Csp3-H oxidations en route to a highly oxidized terpene target. This "oxidase phase" would use a strategic combination of known Csp3-H oxidation techniques, but it would naturally highlight gaps in current methodology, eliciting invention and discovery. Specifically, the ent-atisane and taxane families of diterpenoids were chosen due to their large arrays of oxidative diversity found in Nature, and two methods in Csp3-H functionalization are proposed herein in order to minimize the number of steps and non-strategic redox fluctuations toward their total syntheses. To this end, a hydroxyl-directed desaturation reaction (to act as a "desaturase mimic") and a hydroxyl-directed methyl group hydroxylation reaction (to act as a "hydroxylase mimic") would be developed in the course of these synthetic endeavors. The ent-atisane and taxane families exhibit biological activities in almost every conceivable therapeutic area. Because of its similarity to biosynthesis, the "oxidation level ascent" within these terpene families would naturally lead to the synthesis of related family members and closely related analogs during the pursuit of highly oxidized ent-atisane (e.g., ent-atisenol) and taxane (e.g., Taxol(R)) targets. The scalable, enantioselective synthesis of a lowly oxidized ent-atisane or taxane core similar to the ones employed in Nature, followed by a short series of sequential, site-selective Csp3-H oxidations, would allow for a divergent synthesis that could target large quantities of scarce biologically active natural products and non-natural analogs for use in the fields of cancer, Alzheimer<s and infectious disease. This proposal is organized into three parts: 1) The first section describes the development of a hydroxyl-directed, net dehydrogenation reaction, which would serve useful in the synthetic approach toward both ent-atisanes and taxanes;2) the second part details a short, enantioselective synthesis of the ent-atisane framework, subsequent Csp3-H oxidation sequences en route to various family members, as well as a hydroxyl-directed methyl group hydroxylation reaction, which would allow access to a characteristic syn- 1,3-diol motif that pervades terpenoid frameworks in general;3) the final section describes an efficient enantioselective synthesis of the taxane skeleton for its subsequent use as an oxidase phase substrate, in order to target diverse bioactive taxanes as well as the commercial drug Taxol(R). PUBLIC HEALTH RELEVANCE: The ent-atisane and taxane families exhibit biological activities in almost every conceivable therapeutic area due to its large array of structural diversity. The scalable, enantioselective synthesis of a lowly oxidized ent-atisane or taxane core similar to the ones employed in Nature, followed by sequential, site-selective Csp3-H oxidations, would allow for a divergent synthesis that could target many ent-atisanes and taxanes from common intermediates. This work aims to synthesize large quantities of scarce biologically active natural products and non-natural analogs for use in the fields of cancer, Alzheimer's and infectious disease, as well as to fill gaps in the chemical toolbox of current Csp3-H oxidation techniques.